Control of beta-Sheet Self-Assembly through Chemical Crosslinks

University Of California-Irvine, Irvine CA

Investigators

Abstract

With this award, the Chemistry of Life Processes program is supporting the research of Professor James Nowick of the Department of Chemistry at the University of California, Irvine to design, synthesize and study macrocyclic model systems to better understand peptide assembly and aggregation. While proteins in their folded states have been widely studied by structural biologists, it is becoming increasingly clear that their poorly understood misfolded and aggregated states are also of critical importance in biology. Chemical model systems provide an ideal way to better study these complex states. The model systems being developed here will allow the investigation of edge-to-edge hydrogen bonding and face-to-face hydrophobic interactions, particularly in beta-sheet-like assemblies. Because the model systems are macrocycles that interact in a controlled fashion, it may be possible to use the systems developed here to control and modulate peptidyl secondary structure and eventually protein aggregation. A better understanding of molecular assembly and aggregation in beta-sheet-like structures could have broad scientific impact, well beyond this project, in chemistry and biology. Educational components of this project include the cross-disciplinary training of graduate and undergraduate students in bioorganic and peptide model chemistry. In addition, the PI and his students will continue in their efforts to spark interest in chemistry and science at the K-12 level through the "UCI Chemistry Outreach Program." The PI initiated this program and it has now reached thousands of K-12 students over the past two decades.